Chapter 11 Alcohols and Ethers

Nomenclature Nomenclature of Alcohols (Sec. 4.3F) Nomenclature of Ethers Common Names The groups attached to the oxygen are listed in alphabetical order IUPAC Ethers are named as having an alkoxyl substituent on the main chain Chapter 11

Chapter 11 Cyclic ethers can be named using the prefix oxa- Three-membered ring ethers can be called oxiranes; Four-membered ring ethers can be called oxetanes Chapter 11

Physical Properties of Alcohols and Ethers Ether boiling points are roughly comparable to hydrocarbons of the same molecular weight Molecules of ethers cannot hydrogen bond to each other Alcohols have considerably higher boiling points Molecules of alcohols hydrogen bond to each other Both alcohols and ethers can hydrogen bond to water and have similar solubilities in water Diethyl ether and 1-butanol have solubilites of about 8 g per 100 mL in water Chapter 11

Synthesis of Alcohols from Alkenes Acid-Catalyzed Hydration of Alkenes This is a reversible reaction with Markovnikov regioselectivity Oxymercuration-demercuration This is a Markovnikov addition which occurs without rearrangement Chapter 11

Hydroboration-Oxidation This addition reaction occurs with anti-Markovnikov regiochemistry and syn stereochemistry Chapter 11

Alcohols as Acids Alcohols have acidities similar to water Sterically hindered alcohols such as tert-butyl alcohol are less acidic (have higher pKa values) Why?: The conjugate base is not well solvated and so is not as stable Alcohols are stronger acids than terminal alkynes and primary or secondary amines An alkoxide can be prepared by the reaction of an alcohol with sodium or potassium metal Chapter 11

Conversion of Alcohols into Alkyl Halides Hydroxyl groups are poor leaving groups, and as such, are often converted to alkyl halides when a good leaving group is needed Three general methods exist for conversion of alcohols to alkyl halides, depending on the classification of the alcohol and the halogen desired Reaction can occur with phosphorus tribromide, thionyl chloride or hydrogen halides Chapter 11

Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides The order of reactivity is as follows Hydrogen halide HI > HBr > HCl > HF Type of alcohol 3o > 2o > 1o < methyl Mechanism of the Reaction of Alcohols with HX SN1 mechanism for 3o, 2o, allylic and benzylic alcohols These reactions are prone to carbocation rearrangements In step 1 the hydroxyl is converted to a good leaving group In step 2 the leaving group departs as a water molecule, leaving behind a carbocation Chapter 11

Primary and methyl alcohols undergo substitution by an SN2 mechanism In step 3 the halide, a good nucleophile, reacts with the carbocation Primary and methyl alcohols undergo substitution by an SN2 mechanism Primary and secondary chlorides can only be made with the assistance of a Lewis acid such as zinc chloride Chapter 11

Alkyl Halides from the Reaction of Alcohols with PBr3 and SOCl2 These reagents only react with 1o and 2o alcohols in SN2 reactions In each case the reagent converts the hydroxyl to an excellent leaving group No rearrangements are seen Reaction of phosphorous tribromide to give alkyl bromides Chapter 11

Reaction of thionyl chloride to give alkyl chlorides Often an amine is added to react with HCl formed in the reaction Chapter 11

Tosylates, Mesylates, and Triflates: Leaving Group Derivatives of Alcohols The hydroxyl group of an alcohol can be converted to a good leaving group by conversion to a sulfonate ester Sulfonyl chlorides are used to convert alcohols to sulfonate esters Base is added to react with the HCl generated Chapter 11

A sulfonate ion (a weak base) is an excellent leaving group If the alcohol hydroxyl group is at a stereogenic center then the overall reaction with the nucleophile proceeds with inversion of configuration The reaction to form a sulfonate ester proceeds with retention of configuration Triflate anion is such a good leaving group that even vinyl triflates can undergo SN1 reaction Chapter 11

Synthesis of Ethers Ethers by Intermolecular Dehydration of Alcohol Primary alcohols can dehydrate to ethers This reaction occurs at lower temperature than the competing dehydration to an alkene This method generally does not work with secondary or tertiary alcohols because elimination competes strongly The mechanism is an SN2 reaction Chapter 11

Williamson Ether Synthesis This is a good route for synthesis of unsymmetrical ethers The alkyl halide (or alkyl sulfonate) should be primary to avoid E2 reaction Substitution is favored over elimination at lower temperatures Chapter 11

Synthesis of Ethers by Alkoxymercuration-Demercuration An alcohol is the nucleophile (instead of the water nucleophile used in the analogous reaction to form alcohols from alkenes) tert-Butyl Ethers by Alkylation of Alcohols: Protecting Groups This method is used to protect primary alcohols The protecting group is removed using dilute acid Chapter 11

Silyl Ether Protecting Groups Silyl ethers are widely used protecting groups for alcohols The tert-butyl dimethysilyl (TBDMS) ether is common The protecting group is introduced by reaction of the alcohol with the chlorosilane in the presence of an aromatic amine base such as imidazole or pyridine The silyl ether protecting group is removed by treatment with fluoride ion (e.g. from tetrabutyl ammonium fluoride) Chapter 11

Reactions of Ethers Acyclic ethers are generally unreactive, except for cleavage by very strong acids to form the corresponding alkyl halides Dialkyl ethers undergo SN2 reaction to form 2 equivalents of the alkyl bromide Chapter 11

Epoxides Epoxides are three-membered ring cyclic ethers These groups are also called oxiranes Epoxides are usually formed by reaction of alkenes with peroxy acids This process is called epoxidation and involves syn addition of oxygen Chapter 11

Epoxidation is stereospecfic Magnesium monoperoxyphthalate (MMPP) is a common and safe peroxy acid for epoxidation Epoxidation is stereospecfic Epoxidation of cis-2-butene gives the meso cis oxirane Epoxidation of trans-2-butene gives the racemic trans oxirane Chapter 11

Reaction of Epoxides Epoxides are considerably more reactive than regular ethers The three-membered ring is highly strained and therefore very reactive Acid-catalyzed opening of an epoxide occurs by initial protonation of the epoxide oxygen, making the epoxide even more reactive Acid-catalyzed hydrolysis of an epoxide leads to a 1,2-diol Chapter 11

In unsymmetrical epoxides, the nucleophile attacks primarily at the most substituted carbon of the epoxide Chapter 11

Base-catalyzed reaction with strong nucleophiles (e. g Base-catalyzed reaction with strong nucleophiles (e.g. an alkoxide or hydroxide) occurs by an SN2 mechanism The nucleophile attacks at the least sterically hindered carbon of the epoxide Chapter 11

Anti 1,2-Dihydroxylation of Alkenes via Epoxides Opening of the following epoxide with water under acid catalyzed conditions gives the trans diol Chapter 11

Epoxide ring-opening is a stereospecific process Chapter 11

Chapter 11